Identifying cancer-causing mutations from sequenced cancer genomes hold much promise for targeted therapy and precision medicine. "Driver" mutations are primarily responsible for cancer progression, while "passengers" are functionally neutral. Although several computational approaches have been developed for distinguishing between driver and passenger mutations, very few have concentrated on using the raw nucleotide sequences surrounding a particular mutation as potential features for building predictive models. Using experimentally validated cancer mutation data in this study, we explored various string-based feature representation techniques to incorporate information on the neighborhood bases immediately 5' and 3' from each mutated position. Density estimation methods showed significant distributional differences between the neighborhood bases surrounding driver and passenger mutations. Binary classification models derived using repeated cross-validation experiments provided comparable performances across all window sizes. Integrating sequence features derived from raw nucleotide sequences with other genomic, structural, and evolutionary features resulted in the development of a pan-cancer mutation effect prediction tool, NBDriver, which was highly efficient in identifying pathogenic variants from five independent validation datasets. An ensemble predictor obtained by combining the predictions from NBDriver with three other commonly used driver prediction tools (FATHMM (cancer), CONDEL, and MutationTaster) significantly outperformed existing pan-cancer models in prioritizing a literature-curated list of driver and passenger mutations. Using the list of true positive mutation predictions derived from NBDriver, we identified a list of 138 known driver genes with functional evidence from various sources. Overall, our study underscores the efficacy of using raw nucleotide sequences as features to distinguish between driver and passenger mutations from sequenced cancer genomes.Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor, but it also acts as a substrate for NAD-consuming enzymes, regulating cellular events such as DNA repair and gene expression. Since such processes are fundamental to support cancer cell survival and proliferation, sustained NAD production is a hallmark of many types of neoplasms. Depleting intratumor NAD levels, mainly through interference with the NAD-biosynthetic machinery, has emerged as a promising anti-cancer strategy. NAD can be generated from tryptophan or nicotinic acid. In addition, the "salvage pathway" of NAD production, which uses nicotinamide, a byproduct of NAD degradation, as a substrate, is also widely active in mammalian cells and appears to be highly exploited by a subset of human cancers. In fact, research has mainly focused on inhibiting the key enzyme of the latter NAD production route, nicotinamide phosphoribosyltransferase (NAMPT), leading to the identification of numerous inhibitors, including FK866 and CHS-828. Unfortunately, the clinical activity of these agents proved limited, suggesting that the approaches for targeting NAD production in tumors need to be refined. In this contribution, we highlight the recent advancements in this field, including an overview of the NAD-lowering compounds that have been reported so far and the related in vitro and in vivo studies. We also describe the key NAD-producing pathways and their regulation in cancer cells. Finally, we summarize the approaches that have been explored to optimize the therapeutic response to NAMPT inhibitors in cancer.Fever alone can lead to rare serious complications in children, such as febrile seizures. The aim of this study is to assess the knowledge, beliefs, and behavior of parents toward fever and its management.
A cross-sectional study using an online questionnaire was applied over a period of 3 months, from January to March 2018, to parents who were living in Saudi Arabia. The inclusion criteria were a parent who is a resident of Saudi Arabia, with at least one child aged 6 years or less, while incomplete questionnaires, having a child aged more than 6 years, or parents who were not living in Saudi Arabia were excluded.
A total of 656 parents completed the questionnaire. More than two-thirds of the subjects were female, the majority of whom were aged between 25-33 years old. The best-reported place to measure the temperature of children was the armpit (46%), followed by the ear (28%) and the mouth (10.7%). More than half of the parents considered their children feverish at a temperature of 38 °C. The majority of parents (79.7%) reported that the most serious side effects of fever were seizure, brain damage (39.3%), coma (29.9%), dehydration (29.7%), and death (25%). The most common method used to measure a child's temperature was an electronic thermometer (62.3%). The most common antipyretic was paracetamol (84.5%).
Our study demonstrates the good knowledge of parents in identifying a feverish temperature using the recommended route and tools for measuring body temperature.
Our study demonstrates the good knowledge of parents in identifying a feverish temperature using the recommended route and tools for measuring body temperature.As classrooms become more and more diverse, it is imperative to provide physical education teacher education (PETE) students with opportunities to develop competencies that promote quality education for all students. In this study, PETE students applied a physical education service-learning (SL) program aimed at enhancing Autism Spectrum Disorder (ASD) children's motor domain and general well-being-objectives that are connected to the third focus of the United Nations' Sustainable Development Goals (SDGs). Traditionally, research on SL has focused on students' outcomes, and there is a call to examine SL's effects on service receivers, which is the gap this paper aspires to fill. https://www.selleckchem.com/products/elexacaftor.html The aim of this study was to measure the postural control of children with ASD who were involved in a 6-month SL program in comparison to ASD peers in a control group. A quasi-experimental design was used in which a total of 29 children with ASD participated. The results of the experimental group showed a significant improvement in the vestibular pathways, an improvement trend in the somatosensorial and visual pathways and improvements in the dynamic tests.